Abstract
Gastric cancer is a malignant tumor with a high incidence and mortality rate worldwide. Nevertheless, anticancer drugs that can be used for gastric cancer treatment are limited. Therefore, it is important to develop targeted anticancer drugs for the treatment of gastric cancer. Dehydroabietic acid (DAA) is a diterpene found in tree pine. Previous studies have demonstrated that DAA inhibits gastric cancer cell proliferation by inducing apoptosis. However, we did not know how DAA inhibits the proliferation of gastric cancer cells through apoptosis. In this study, we attempted to identify the genes that induce cell cycle arrest and cell death, as well as those which are altered by DAA treatment. DAA-regulated genes were screened using RNA-Seq and differentially expressed genes (DEGs) analysis in AGS cells. RNA-Seq analysis revealed that the expression of survivin, an apoptosis inhibitor, was significantly reduced by DAA treatment. We also confirmed that DAA decreased survivin expression by RT-PCR and Western blotting analysis. In addition, the ability of DAA to inhibit survivin was compared to that of YM-155, a known survivin inhibitor. DAA was found to have a stronger inhibitory effect in comparison with YM-155. DAA also caused an increase in cleaved caspase-3, an apoptosis-activating protein. In conclusion, DAA is a potential anticancer agent for gastric cancer that inhibits survivin expression.
Highlights
We demonstrated that Dehydroabietic acid (DAA) treatment inhibited the proliferation of gastric cancer cells
We demonstrated that DAA effectively inhibited survivin expression through RNASeq results
AGS cells were treated with DAA, and survivin expression was confirmed by RT-Polymerase Chain Reaction (PCR) and Western blotting (Figure 3A)
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. DAA-induced cell cycle arrest and apoptosis induction in gastric cancer were demonstrated [8]. We tried to determine the genes regulated by DAA that inhibit the proliferation of gastric cancer cells. Cell death caused by these factors induces an inflammatory response [9,10]. Apoptosis is a process of programmed cell death. Apoptosis does not cause damprocess of programmed cell death. Survivin negatively programmed cellIn death or apoptosis is inhibiting encoded bycaspase. Survivin negatively regulatesofprogrammed cell helps death cancer or apoptosis by [14,15]. RNA-Seq was performed to identify the gene that inhibits the proliferation gastric cancer cells. IAP family member survivin was discovered through of gastric cancer. DEG analysis, and it was suggested that DAA is a specific inhibitor of survivin
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